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K J Netter

Publications and source records attributed to K J Netter.

At least 91 records · Page 5Linked to original sources

Measurement of substrate-induced oxygen uptake during microsomal drug oxidation using a gold micro-electrode.

1. A resin-coated gold micro-electrode has been used for polarographic determination of oxygen concentration in liver microsomal suspensions from phenobarbital-pretreated rats. 2. The rate of oxygen uptake on addition of an NADPH-regenerating system and the rate after addition of various substrates of the mixed function oxidase system were measured. The rate of oxygen uptake was faster in the presence of substrate than in the presence of NADPH alone. 3. Kinetic constants (Km and V max) for biphenyl, hexobarbital, ethylmorphine, naphthalene and SKF 525-A measured by this technique compare favourably with those obtained either by measurements of NADPH oxidation, or chemical measurements of substrate disappearance or product formation. 4. The practical applications of the gold electrode to drug metabolism studies are discussed.

Animals↗

[Drug metabolism in early life].

For various reasons the dosage of drugs in early life is difficult and complicated. Besides differences in sensitivity of pharmacological receptors, in protein binding of drugs and in drug distribution the metabolic elimination of drugs has to be considered as playing an important role for the understanding of the pharmacotherapeutic peculiarities of the perinatal period. The most important means for chemical inactivation of drugs are oxidation and conjugation of these foreign compounds. Both pathways will be briefly outlined. Evidence for a decreased ability of infants to oxidize drugs can be found in the observation that the biological half lives of amobarbital and other drugs are about twice as long as those of the mother. Retarded conjugation in infants manifests itself especially with sulfonamides. The postnatal development of the drug oxidizing enzyme system is described with special emphasis on the development of cytochrome P450 in young pigs. In this context it is of interest that the apoenzyme of the mixed function hydroxylase seems to be present already before the iron containing haem moiety is fitted into the enzyme molecule. Furthermore it is described that the postnatal development of the glucuxonyl transferase is different for different substrates.

Amobarbital↗